Abstract
To study the cyclooxygenase 2 (Cox 2) expression in newly diagnosed plasma cell myeloma cases by immunohistochemistry (IHC) and correlate with clinicohematological characteristics. Immunohistochemical expression of Cox 2 on bone marrow trephine biopsy was studied in seventy-three newly diagnosed myeloma cases [56 males, 17 females, median age; 58 years (36–75)] and fifteen controls using SP21 clone antibody. A median immuno-score (proportion x intensity) stratified the entire cohort into low and high expressors. Cox 2 immunoexpression was compared and correlated with clinicolaboratory characteristics and marrow histomorphology and survival. Twenty one of 73 (38.7%) cases had a plasmablastic morphology whereas remainder fifty-two (61.3%) had a differentiated morphology. The Cox 2 expression was noted in 71/73 (97.2%) cases (median score = 127.3) and 15/15 (100%) controls. Low expressors was associated with higher circulating plasma cells, increased marrow tumor burden, blastic morphology, and lower proliferation index (p < 0.05) with a peculiar ‘dot-block’ cytoplasmic positivity (p < 0.001); whereas high expressors had thinned out bony trabeculae with granular cytoplasmic positivity with or without membrane accentuation (p < 0.001). Cox 2 expression had a weak negative correlation with tumor burden (r; -0.32, p = 0.01) and positive correlation with proliferation index (r; 0.29, p = 0.03). There was no statistically significant difference in the survival between low (n = 20) and high (n = 23) expressors (log rank p = 0.11). A high proportion of myeloma cells in our cohort expressed Cox 2 using SP21 clone; and this may have a role in futuristic research and therapy.
Similar content being viewed by others
References
Bernard MP, Bancos S, Sime PJ, Phipps RP (2008) Targeting cyclooxygenase-2 in hematological malignancies: rationale and promise. Curr Pharm Des 14:2051–2060
Bernard MP, Phipps RP (2010) Inhibition of cyclooxygenase-2 impairs the expression of essential plasma cell transcription factors and human B-lymphocyte differentiation. Immunology 129:87–96
Sobolewski C, Cerella C, Dicato M, Ghibelli L, Diederich M (2010) The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. Int J Cell Biol. https://doi.org/10.1155/2010/215158
Giles FJ, Kantarjian HM, Bekele BN, Cprtes JE, Faderl S, Thomas DA et al (2002) Bone marrow cyclooxygenase-2 levels are elevated in chronic-phase chronic myeloid leukemia and are associated with reduced survival. Br J Hematol 119:38–45
Hazar B, Ergin M, Seyrek E, Erdogan S, Tuncer I, Hakverdi S (2004) Cyclooxygenase-2 (Cox-2) expression in lymphomas. Leuk Lymphoma 45:1395–1399
Lee SF, Ng TY, Wong FCS, Tung SY (2017) Aspirin and risk of multiple myeloma in adults. A systematic review and meta-analysis. Leuk Res Rep 7:23–28
Ladetto M, Vallet S, Trojan A, Dell’Aquila M, Monitillo L, Rosato R et al (2005) Cyclooxygenase-2 (Cox-2) is frequently expressed in multiple myeloma and is an independent predictor of poor outcome. Blood 105:4784–4791
Cetin M, Buyukberber S, Demir M, Sari I, Sari I, Deniz K et al (2005) Overexpression of cyclooxygenase- 2 in multiple myeloma: association with reduced survival. Am J Hematol 80:169–173
Trojan A, Tinguely M, Vallet S, Seifert B, Jenni B, Zippelius A et al (2006) Clinical significance of cyclooxygenase-2 (Cox-2) in multiple myeloma. Swiss Med Wkly 136:400–403
Owen RG, Fan I, O’connor SJ, Rollett RA, Anthony CJ, Davies FE et al (2007). Cyclooxygenase- 2 (Cox-2) in multiple myeloma: prognostic factor or therapeutic target. Br J Haematol 136:163–164.
Kast RE (2006) Aspirin use in myeloma: a note of caution regarding potential tumour necrosis factor elevation. British J Haematol 133:216
Vural F, Soyer N, Hekimgil M, Cagirgan S, Donmez A, Tombuloglu M (2014) The association between Cox-2 expression and survival in myeloma patients. Eur Rev Med Pharma Sci 18:2132–2136
Khan R, Sharma M, Kumar L, Husain SA, Sharma A (2013) Interrelationship and expression profiling of cyclooxygenase and angiogenic factors in Indian patients with multiple myeloma. Ann Hematol 92:101–109
Khan R, Sharma M, Kumar L, Husain SA, Sharma A (2016) Cinnamon extract exhibits potent anti-proliferative activity by modulating angiogenesis and cyclooxygenase in myeloma cells. J Herb Med 6:149–156
Nasir A, Boulware D, Kaiser HE, Lancaster JM, Coppola D, Smith PV et al (2007) Cyclooxygenase-2 (COX-2) expression in human endometrial carcinoma and precursor lesions and its possible use in cancer chemoprevention and therapy. Vivo 21:35–43
Tripodo C, Florena AM, Porcasi R, Ingrao S, Guarnotta C, Franco V (2007) Constant detection of cyclooxygenase 2 in terminal stages of myeloid maturation. Acta Haematol 117:48–50
Shimozuma J, Takimoto M, Maeda T, Honma M, Shiozawa E, Yamochi T et al (2007) Correlation between expression of cyclooxygenase-2 and angiogenesis in multiple myeloma. J Showa Med Asso (Japan) 67(3):182–189
Que W, Li S, Chen J (2013) NS-398 enhances the efficacy of bortezomib against RPMI8226 human multiple myeloma cells. Molecular Medicine Rep 7:1641–1645
Zhang M, Abe Y, Matsushima T, Nishimura J, Nawata H, Muta K (2005) Selective cyclooxygenase 2 inhibitor NS-398 induces apoptosis in myeloma cells via a Bcl-2 independent pathway. Leuk Lymphoma 46:425–433
Prince HM, Mileshkin L, Roberts A, Ganju V, Underhill C, Catalano J et al (2005) A multicenter phase II trial of thalidomide and celecoxib for patients with relapsed and refractory multiple myeloma. Clin Cancer Res 11:5504–5514
Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Khan KN, Masferrer J et al (2000) COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89:2637–2645
Remmele W, Schicketanz K-H (1993) Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS). Pathol Res Pract 8:227–245
Acknowledgements
The authors would like to thank the contribution made by Sk Samiur Raheman, Jaydev Patra, and Nihar Ranjan Das of Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar for their technical assistance in carrying out immunohistochemistry in all the cases. Also, the authors would like to thank Vasundhara Raina, PDF, Department of Clinical Hematology and Laboratory Sciences, Tata Medical Center, Kolkata for her statistical assistance.
Funding
None.
Author information
Authors and Affiliations
Contributions
SAP: Data collection, analysis and interpretation of data, literature review, and writing of first manuscript draft. SP: Conceptual design, literature review, data acquisition and interpretation, review of manuscript for intellectual content. AP: Provided the data pertaining to clinical and lab investigation, management and follow up, and reviewed the manuscript for intellectual content. GS: did statistical analyses.
Corresponding author
Ethics declarations
Conflict of interest
The authors declared that they have no conflict of interest.
Ethics Approval
The Institutional Ethics Committee at All India Institute of Medical Sciences, Bhubaneswar approved the study protocol, and this study was conducted in accordance with the Declaration of Helsinki.
Consent of Publication
This manuscript was presented, in part, as an Oral Paper for JC Patel Oration Award session at 60th National Annual Conference of Indian Association of Hematology and Blood Transfusion (ISHBT), held at New Delhi, India during November 2019.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Pattnaik, S.A., Padhi, S., Panigrahi, A. et al. Cyclooxygenase 2 (Cox 2) Expression in Newly Diagnosed Plasma Cell Myeloma: A Clinicopathological and Immunohistochemical Study on 73 Cases from a Single Tertiary Care Center. Indian J Hematol Blood Transfus 38, 235–245 (2022). https://doi.org/10.1007/s12288-021-01448-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12288-021-01448-3